Journal Article

DZNE-2021-01569

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Early IFN-α signatures and persistent dysfunction are distinguishing features of NK cells in severe COVID-19.

Krämer, B. ; Knoll, R.DZNE* ; Bonaguro, L.DZNE* ; ToVinh, M. ; Raabe, J. ; Astaburuaga-García, R. ; Schulte-Schrepping, J.DZNE* ; Kaiser, K. M. ; Rieke, G. J. ; Bischoff, J. ; Monin, M. B. ; Hoffmeister, C. ; Schlabe, S. ; De Domenico, E.DZNE* ; Reusch, N.DZNE* ; Händler, K.DZNE* ; Reynolds, G. ; Blüthgen, N. ; Hack, G. ; Finnemann, C. ; Nischalke, H. D. ; Strassburg, C. P. ; Stephenson, E. ; Su, Y. ; Gardner, L. ; Yuan, D. ; Chen, D. ; Goldman, J. ; Rosenstiel, P. ; Schmidt, S. V. ; Latz, E.Extern* ; Hrusovsky, K. ; Ball, A. J. ; Johnson, J. M. ; Koenig, P.-A. ; Schmidt, F. I. ; Haniffa, M. ; Heath, J. R. ; Kümmerer, B. M. ; Keitel, V. ; Jensen, B. ; Stubbemann, P. ; Kurth, F. ; Sander, L. E. ; Sawitzki, B. ; Initiative, D. C. O. (Collaboration Author) ; Aschenbrenner, A. C.Extern* ; Schultze, J.Extern* ; Nattermann, J. ; Altmüller, J. ; Angelov, A. ; Aschenbrenner, A. C.Extern* ; Bals, R. ; Bartholomäus, A. ; Becker, A. ; Becker, M. K. H.Extern* ; Bezdan, D. ; Bitzer, M. ; Blumert, C. ; Bonifacio, E. ; Bork, P. ; Boyke, B. ; Blum, H. ; Casadei, N. ; Clavel, T. ; Colome-Tatche, M. ; Cornberg, M. ; De La Rosa Velázquez, I. A. ; Diefenbach, A. ; Dilthey, A. ; Fischer, N. ; Förstner, K. ; Franzenburg, S. ; Frick, J.-S. ; Gabernet, G. ; Gagneur, J. ; Ganzenmueller, T. ; Gauder, M. ; Geißert, J. ; Goesmann, A. ; Göpel, S. ; Grundhoff, A. ; Grundmann, H. ; Hain, T. ; Hanses, F. ; Hehr, U. ; Heimbach, A. ; Hoeper, M. ; Horn, F. ; Hübschmann, D. ; Hummel, M. ; Iftner, T. ; Iftner, A. ; Illig, T. ; Janssen, S. ; Kalinowski, J. ; Kallies, R. ; Kehr, B. ; Keller, A. ; Keppler, O. T. ; Kim-Hellmuth, S. ; Klein, C. ; Knop, M. ; Kohlbacher, O. ; Köhrer, K. ; Korbel, J. ; Kremsner, P. G. ; Kühnert, D. ; Kurth, I. ; Landthaler, M. ; Li, Y. ; Ludwig, K. U. ; Makarewicz, O. ; Marini, F. ; Marz, M. ; McHardy, A. C. ; Mertes, C. ; Münchhoff, M. ; Nahnsen, S. ; Nöthen, M.Extern* ; Ntoumi, F. ; Nürnberg, P. ; Ossowski, S. ; Overmann, J. ; Peter, S. ; Pfeffer, K. ; Pink, I. ; Poetsch, A. R. ; Protzer, U. ; Pühler, A. ; Rajewsky, N. ; Ralser, M. ; Reiche, K. ; Rieß, O. ; Ripke, S. ; Nunes da Rocha, U. ; Rosenstiel, P. ; Saliba, A.-E. ; Sander, L. E. ; Sawitzki, B. ; Scheithauer, S. ; Schiffer, P. ; Schmid-Burgk, J. ; Schneider, W. ; Schulte, E.-C. ; Schultze, J.Extern* ; Sczyrba, A. ; Sharaf, M.Extern* ; Singh, Y. ; Sonnabend, M. ; Stegle, O. ; Stoye, J. ; Theis, F. ; Ulas, T.Extern* ; Vehreschild, J. ; Velavan, T. P. ; Vogel, J. ; Volland, S. ; von Kleist, M. ; Walker, A. ; Walter, J. ; Wieczorek, D. ; Winkler, S. ; Ziebuhr, J.

2021
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.immuni.2021.09.002

Abstract: Longitudinal analyses of the innate immune system, including the earliest time points, are essential to understand the immunopathogenesis and clinical course of coronavirus disease (COVID-19). Here, we performed a detailed characterization of natural killer (NK) cells in 205 patients (403 samples; days 2 to 41 after symptom onset) from four independent cohorts using single-cell transcriptomics and proteomics together with functional studies. We found elevated interferon (IFN)-α plasma levels in early severe COVD-19 alongside increased NK cell expression of IFN-stimulated genes (ISGs) and genes involved in IFN-α signaling, while upregulation of tumor necrosis factor (TNF)-induced genes was observed in moderate diseases. NK cells exert anti-SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) activity but are functionally impaired in severe COVID-19. Further, NK cell dysfunction may be relevant for the development of fibrotic lung disease in severe COVID-19, as NK cells exhibited impaired anti-fibrotic activity. Our study indicates preferential IFN-α and TNF responses in severe and moderate COVID-19, respectively, and associates a prolonged IFN-α-induced NK cell response with poorer disease outcome.

Keyword(s): Base Sequence (MeSH) ; COVID-19: immunology (MeSH) ; Humans (MeSH) ; Immunity, Innate: immunology (MeSH) ; Inflammation: immunology (MeSH) ; Interferon-alpha: blood (MeSH) ; Interferon-alpha: immunology (MeSH) ; Killer Cells, Natural: immunology (MeSH) ; Pulmonary Fibrosis: pathology (MeSH) ; RNA-Seq (MeSH) ; SARS-CoV-2: immunology (MeSH) ; Severity of Illness Index (MeSH) ; Transcriptome: genetics (MeSH) ; Tumor Necrosis Factor-alpha: metabolism (MeSH) ; United Kingdom (MeSH) ; United States (MeSH) ; COVID-19 ; NK cells ; TNF ; antiviral ; lung fibrosis ; moderate ; proteomics ; scRNA-seq ; severe ; type 1 IFN ; IFNA1 protein, human ; Interferon-alpha ; Tumor Necrosis Factor-alpha

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Contributing Institute(s):

1. Platform for Single Cell Genomics and Epigenomics (Schultze - PRECISE)
2. Platform for Single Cell Genomics and Epigenomics at DZNE & University of Bonn (R&D PRECISE)

Research Program(s):

1. 354 - Disease Prevention and Healthy Aging (POF4-354) (POF4-354)

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 40 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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